Organophosphines

ABSTRACT

Organophosphines of the formula (R) a P(H) 3−a ( where R is C1-C20 alkyl, alkenyl, alkaryl or styryl and a is 1, 2, or 3) are produced by (i) reacting a tris(hydroxyorgano)phosphine (THP) with an organic halogen containing compound; (ii) reacting the product of (i) with a base; (iii) removing aldehydes from the product of (ii) and adding an organic phase, followed by distillation or phase-separation to obtain the desired product.

This application is a U.S. National Phase Application under 35 USC 371of International Application PCT/GB99/03482 (published in English) filedOct. 21, 1999.

This invention relates to a method for the production of primary,secondary or tertiary phosphines and to phosphines obtained from theaforesaid method.

In particular, the present invention relates to the preparation oforganophosphines of the formula R_((a))PH_((3−a)) where R is an organicgroup and a is 1, 2 or 3.

Organophosphines are used as intermediates in the synthesis of a widerange of organophosphorus fine chemicals, including pesticides andpharmaceuticals. One conventional method of preparing alkylphosphinesinvolves the use of high-pressure phosphine. This is a hazardousoperation and requires a special plant which is expensive to install,expensive to maintain and expensive to operate safely. Moreover, thistechnology is used to manufacture tri-alkyl phosphines. Primary andsecondary phosphines are not readily accessible by this method.

A more selective alkylation of phosphine can be achieved by reactingGrignard reagents with phosphorus halides, followed by reduction with,for example, lithium aluminium hydride. However, this approach isgenerally unsuitable for commercial production on account of the highcost of the reagents.

Primary and secondary phosphines can also be prepared by thermaldisproportionation of alkyl- or dialkyl-phosphonous acids. Such routeshave low yields.

We have now discovered that primary, secondary or tertiary phosphinescan be prepared by way of a convenient reaction using relatively lowcost reagents and standard pressures. In particular we found that thereaction can be made to yield specific mono-, di-, or tri-alkylphosphines in high yield, or desired mixtures of the phosphines.

Accordingly, the present invention provides a method for the productionof a primary, secondary or tertiary phosphine having the general formula(R)_(a)P(H)_(3−a), where a is 1, 2 or 3, in which the method comprisesthe following stages:

(i) reacting a tris(hydroxyorgano)phosphine (THP) with an organichalogen-containing compound;

(ii) reacting the product of stage (i) with a base;

(iii) removing aldehydes from the product of stage (ii) and adding anorganic phase, followed by distillation or phase-separation to obtainthe desired phosphine.

Preferably, the THP has its hydroxy group on the carbon atom which isjoined to the phosphorus atom.

Preferably, the removal of aldehydes from the product of stage (ii) isachieved by the addition of sodium sulphite.

The present invention also provides a primary, secondary or tertiaryphosphine made by the method described in the immediately-precedingparagraph. Such phosphines include, for example, 1,2-diphosphino-ethane,diethylphosphine and tri-n-butyl phosphine.

Preferably, in stage (i), there is present a stoichiometric excess ofthe organic halogen-containing compound, relative to the THP. Forexample, the halogen-containing compound may be present in an amount ofup to 10:1, for example 2:1 to 3:1, relative to the THP.

Stage (i) is preferably carried out at a temperature of less than 90°,at ambient pressure. Stage (i) may be carried out in an inert (e.g.nitrogen or argon) atmosphere. Stage (i) is preferably carried out inthe presence of a solvent. The solvent may be water or a water/alcoholmixture, sufficient to solubilise the organic halogen-containingcompound and to achieve a practical reaction-rate.

The organic halogen-containing compound may suitably have the generalformula R(X)_(n), where R represents an alkyl, alkenyl, alkaryl, alkynylor styryl group of from 1 to 20 (preferably 2 to 8) carbon atoms, Xrepresents a halogen (e.g. chlorine, bromine or iodine—preferablybromine) atom and n is a whole number of from 1 to 4, the group R havingat least one aliphatic carbon atom adjacent the or each halogen atom.

For example, the organic halogen-containing compound may be ethylbromide, butyl bromide, 1,2-dibromo-ethane or 1,3-dibromopropane.

The group R may further include one or more ether-or amino-linkages. Thebase used in stage (ii) may be, for example, sodium hydroxide orpotassium hydroxide.

The aldehyde-removing agent used in stage (iii) may be, for example,sodium sulphite. During stage (iii), the pH of the reaction mixture ispreferably maintained at 6.0 to 8.0 by the addition of an acid such ashydrochloric acid or phosphoric acid or a suitable organic acid such asacetic acid.

The organic phase added to the reaction mixture during stage (iii) maybe a mineral oil (such as paraffin oil) or a petroleum ether of suitableboiling-point range (for example 100-120° C.).

While the reaction which is the subject of the present invention hasbeen described herein with particular reference to the use atris(hydroxyogano) phosphine (THP) as the starting material, it is alsopossible to obtain the THP in situ by reacting atetrakis(hydroxyalkyl)phosphonium salt with a base. For example,tris(hydroxymethyl)phosphine can be produced in situ by reactingtetrakis(hydroxymethyl)phosphonium chloride (THPC) ortetrakis(hydroxymethyl)phosphonium sulphate (THPS) with sodiumhydroxide.

The invention will be illustrated by way of the following examples.

EXAMPLE 1 (1A) Preparation of tri-n-butylphosphine (First Method)

This reaction was carried out in a nitrogen atmosphere, all reactantshaving been purged with nitrogen before use.

(a) A 12-liter reactor was charged withtetrakis(hydroxymethyl)phosphonium chloride (986 g, 4 mole) and ethanol(838 g, 18 mole) and purged with nitrogen for 15 minutes.

(b) A solution of sodium hydroxide (160 g, 4 mole) in water (160 g) wasadded to the reactor over 1.5 hours, keeping the temperature below 20°C. and the pH below 8.

 At the end of this addition, N.M.R. analysis of the product indicated:

tetrakis(hydroxymethyl)phosphonium chloride 5.2%tetrakis(hydroxymethyl)phosphonium oxide 0.7%tris(hydroxymethyl)phosphine 94.1% 

(c) n-Butyl bromide (1640 g, 12 mole) was added, the mixture heated to65° C. and held at that temperature for 4 hours. The mixture was thencooled to the ambient temperature, when N.M.R. analysis showed:

tetrakis(hydroxymethyl)phosphonium chloride 15.7% butylphosphoniumcompounds 78.3% tris(hydroxymethyl)phosphine   6%

(d) A further solution of sodium hydroxide (160 g, 4 mole) in water (160g) was added to the reactor over 1.5 hours, keeping the temperaturebelow 20° C. and the pH below 8. The mixture was then heated to 65° C.for 5 hours. N.M.R. analysis of the product showed:

tris(hydroxymethyl)butylphosphonium ion 16.8%bis(hydroxymethyl)dibutylphosphonium ion 54.3%mono(hydroxymethyl)tributylphosphonium ion   22%tris(hydroxymethyl)phosphine   2% tetrakis(hydroxymethyl)phosphoniumoxide   4%

(e) A further solution of sodium hydroxide (80 g, 2 mole) in water (80g) was added over 1 hour, keeping the temperature below 20° C.

 The mixture was then heated to 65° C. for 3 hours. N.M.R. analysisshowed:

tris(hydroxymethyl)butylphosphonium ion  3.8%bis(hydroxymethyl)dibutylphosphonium ion 41.4%mono(hydroxymethyl)tributylphosphonium ion 47.5%tetrakis(hydroxymethyl)phosphonium oxide  4.2%

(f) The reaction mixture obtained from (e) above was subjected tovacuum-stripping to remove volatile organic components. Water (2.5 l )and petroleum ether (250 ml, b.p. 100-120° C.) were added to the mixtureto produce a two-phase system, followed by solid sodium sulphite (2000g) which caused the pH of the mixture to rise to 11.5. The pH wasreduced to 6.5 by the addition of concentrated hydrochloric acid over 3hours and the mixture was then heated to 45° C. The pH was maintained at6.5 over the next 18 hours, more hydrochloric acid being added asrequired.

 N.M.R. analysis showed:

hydroxymethylphosphines 0.9% tributylphosphine 50.2%  dibutylphosphine 45% monobutylphosphine 3.2%

(g) The phases were separated and the organic phase transferred to apressure-reactor, which was pressurised with butene to 15-20 p.s.i. Anazo-initiator, used as a source of free radicals, was pumped into thereactor each hour for about 20 hours. The butylation stage reduced theamount of dibutylphosphine from 45% to less than 1%.

(h) After vacuum-stripping to remove volatile organic components, thetributylphosphine was distilled under vacuum. The yield (based onphosphorus) was about 65% of theoretical and the purity of the productwas found to be over 98%.

(1B) Preparation of tri-n-butyl phosphine (Second Method)

(a) A 5-liter jacketed reactor was charged with tetrakis-(hydroxymethyl)phosphonium chloride (507 g, 2 mole) and ethanol (500 ml) and purgedwith nitrogen for 15 minutes.

(b) A solution of sodium hydroxide (80 g, 2 mole) in water (80 g) wasadded to the reactor over 1.5 hours, keeping the temperature below 20°C. and the pH below 8.

(c) n-Butyl bromide (685 g, 5 mole) was added over 1 hour while heatingto 65° C. then heating for a further 3 hours. At the end of this time,N.M.R. analysis showed:

tetrakis(hydroxymethyl)phosphonium chloride 15.4%tetrakis(hydroxymethyl)phosphonium oxide  0.7% butylphosphoniums   74%tris(hydroxymethyl)phosphine   9%

(d) A further solution of sodium hydroxide (120 g, 3 mole) in water (120g) was charged to a dropping-funnel and added to the mixture over 5hours at 65° C., the pH being kept below 9 throughout. Heating wascontinued for a further 1.5 hours.

 N.M.R. analysis showed:

tetrakis(hydroxymethyl)phosphonium oxide  4.5%mono(hydroxymethyl)tributylphosphonium ion 16.6%bis(hydroxymethyl)dibutylphosphonium ion 72.2%tris(hydroxymethyl)butylphosphonium ion  0.3%tris(hydroxymethyl)phosphine   5%

(e) After vacuum-stripping to remove volatile organic components, water(1.2l) and petroleum ether 120 ml, b.p. 100-120° C., were added to themixture to produce a two-phase system, followed by solid sodium sulphite(1008 g) at 30° C., causing the pH of the mixture to rise to 10.Concentrated hydrochloric acid was added, in 5-ml portions, over thenext 12 hours. The final pH of the mixture was 6.2. At this stage,N.M.R. analysis of the organic phase showed:

tributylphosphine 15.6% dibutylphosphine 71.4% monobutylphosphine  5.5%mono(hydroxymethyl)dibutylphosphine less than 1%

 The aqueous phase was removed from the reactor and the organic phasewashed twice with water before being transferred to a pressure reactor.

(f) Pressurisation with butene was carried out as described in thecorresponding stage of Example 1A (above). The yield (based onphosphorus) was about 75% of theoretical and the purity of the productwas found to be over 98%.

EXAMPLE 2 Preparation of diethylphosphine

(a) Tetrakis(hydroxymethyl)phosphonium chloride (600 g, 3 moles) andethanol (600 ml, 13 mole) were charged to a 5-liter jacketed reactor. Asolution of sodium hydroxide (97 g, 2.4 mole) in water (97 g) was addedover 70 minutes, keeping the pH of the mixture below 8 and thetemperature below 20° C.

(b) Ethyl bromide (793 g, 7 mole) was added and the mixture heated toabout 40° C. for 3 hours. The pH of the mixture dropped slowly duringthat time, the final pH being 7.21.

(c) A further solution of sodium hydroxide (123 g. 3 mole) in water (123g) was charged to a dropping funnel, sufficient of the solution beingadded to the reactor to raise the pH to 7.5. This pH was maintained for1 hour. The pH was raised, by the addition of sodium hydroxide solution,by 0.5 per hour, so that after a further 6 hours the pH of the mixturewas 10.5. At this stage, N.M.R. analysis showed:

mono(hydroxymethyl)triethylphosphonium ion 13.5%bis(hydroxymethyl)diethylphosphonium ion 75.5%tris(hydroxymethyl)ethylphosphonium ion  2.8%tris(hydroxymethyl)phosphine   7% tetrakis(hydroxymethyl)phosphoniumoxide less than 1%

(d) Unreacted ethyl bromide and ethanol were removed under vacuum at 40°C.

(e) Water (500 ml) and mineral oil (250 ml) were added to the reactor toform a two-phase system. A distillation apparatus was fitted to thereactor. Solid sodium sulphite (1000 g) was added, the pH of the mixturerising to 10.8. The pH was reduced to 7 by the gradual addition ofconcentrated hydrochloric acid. The mixture was then heated to 115° C.to distil out a mix of water and diethylphosphine. The pH was kept at 8by addition of further hydrochloric acid to the reactor. The total timefor this stage was about 7 to 14 hours. The yield (based on phosphorus)was about 50% of theoretical.

 Analysis of the final product showed it to be a mixture comprising:

diethylphosphine and 85% triethylphosphine 15%

EXAMPLE 3 Preparation of 1,2-diphosphinoethane

1,2-diphosphinoethane (BPE) was prepared fromtetrakis(hydroxmethyl)phosphonium chloride (THPC) as follows:

All reactions were carried out under a nitrogen atmosphere in a 2-literround-bottomed flask.

(a) THPC (200 g aqueous solution, 154.0 g actives, 0.808 moles) wascharged to the reaction vessel, together with ethanol (600 ml). Sodiumhydroxide solution (29.1 g, dissolved in 30.0 g water) was added slowlyvia a dropping funnel, keeping the temperature below 27° C. Thisgenerated tris(hydroxymethyl)phosphine (THP). 1,2-Dibromoethane (50.7 g,0.27 moles) was added and the reaction mixture heated at reflux for 4.5hours. A further addition of sodium hydroxide solution (10.0 g, in 10.0g water) was made at this point and the reaction mixture heated for afurther 6.5 hours. The ethanol was then stripped out under vacuum,leaving a viscous residue. ³¹P N.M.R. analysis of the residue showed32.2 mole % conversion to the desired phosphonium intermediate.

(b) The residue from (a) above was diluted with water (250 ml,de-gassed) and the pH adjusted to 7.5. Petroleum ether (300ml) and solidsodium sulphite was added (408.0 g, 3.23 moles) and the pH of thereaction mixture was re-adjusted back to 7.0 by the addition ofconcentrated hydrochloric acid. The mixture was stirred and heated at40° C. for 12 hours, further concentrated hydrochloric acid (ca. 40 ml)being added slowly in order to maintain the pH between 6.5-7.0 ³¹PN.M.R. analysis of the petroleum ether layer at this point showed thepresence of BPE product.

EXAMPLE 4 Synthesis of diethyl phosphine

All reactions were carried out in a 10-liter jacketed reactor fittedwith a dropping-funnel, a temperature probe, a condenser and a glasspH-electrode. The reactions were carried out under a nitrogenatmosphere.

(a) THPC (1500 g of 75% w/w aqueous solution, 6 moles) and ethanol (1500ml) were charged to the reactor. A solution of sodium hydroxide (243 g,6 moles) in water (243 g) was added to the reactor over about 2 hours,keeping the pH below 8 and the temperature below 25° C.

(b) Ethyl bromide (2000 g, 18 moles) was added. The mixture was heatedto about 40° C. for 3 to 4 hours, then left overnight.

(c) The mixture was re-heated to 40° C. A solution of sodium hydroxide(310 g, 7.7 moles) in water (310 g) was charged to the dropping funneland sufficient of this solution added to the contents of the reactor tobring the pH to 7.5. This pH was maintained for 45 minutes, then raised(by addition of the sodium hydroxide solution) to 8.0 for a further 45minutes, then to 8.5 for 45 minutes. The addition was continued at thesame rate until all the sodium hydroxide solution had been added. Atthat stage (with the pH about 10.5) heating was continued for a further2 hours. A distillation apparatus was fitted to the reactor: ethanol andany remaining ethyl bromide were removed under vacuum with the aid of aTEFLON®-lined pump.

 ³¹P N.M.R. analysis at this time showed:

mono(hydroxymethyl)triethylphosphonium ion 20%bis(hydroxymethyl)diethylphosphonium ion 75%tris(hydroxymethyl)ethylphosphonium ion  5%

(d) Water (2500 ml) and mineral oil (600 ml) were added to the mixture,followed by solid sodium sulphite (2500 g, 20 moles). The pH of themixture rose to about 11 and was then slowly lowered by addition ofconcentrated phosphoric acid. The mixture was then heated to 115° C. todistil out an azeotropic mixture of water and diethyl phosphine.Phosphoric acid was added to the reactor whenever the pH of the contentsrose above 8. This stage took 2 days to complete. The phases in thereceiver were separated, producing a mixture comprising:

diethylphosphine about 75% triethylphosphine about 15%mono(hydroxymethyl)diethylphosphine about 10%bis(hydroxymethyl)ethylphosphine

 The weight of the mixture was 500 g, corresponding to a yield of about70% theoretical.

(e) Acetic acid (25%, 500 ml) was added to the receiver and stirred for10 minutes. The water layer was removed and the organic layer washedwith water (500 ml).

 ³¹P N.M.R. analysis of the organic layer showed the purity of thediethyl phosphine to be greater than 95%.

EXAMPLE 5 Coupling of diethyl phosphine Route (I)

All reactions were carried out under an argon atmosphere in a 5-literjacketed reactor fitted with a dropping funnel, a temperature probe anda condenser.

(A) 95% pure diethylphosphine (400 g, 4.2 moles) and t-butylmethyl ether(1000 ml) were charged to the reactor and cooled to below 0° C.Butyllithium (2620 ml, 4.2 moles) in hexames (1.6 molar, ex Aldrich) wasadded over 2-3 hours, the temperature being kept below 0° C. A yellow,slightly cloudy solution was obtained. Some of the mixture was quenchedwith D₂ 0 in an N.M.R. tube, to check conversion. More butyllithium wasadded as required.

(b) 1,2-dichloroethane (205 g, 2.1 moles) was diluted with t-butylmethylether (500 ml) and slowly added to the reactor over 2-3 hours, thetemperature being kept below 0° C. A white solid formed during thisstage. The mixture was heated to reflux for 1 hour, then quenched withwater (500 ml).

(c) To remove the unwanted by-product (tetraethyl diphosphine, about 10%of the mixture) air was admitted to the reactor head space (4-5 times,checked by ³¹P N.M.R.). The water layer was removed, then the solventswere distilled off. The remaining slightly yellow oil was washed withwater (500 ml) and then transferred to a distillation apparatus fittedwith a fractionating column and distilled as described in Example 4above. The product consisted of a colourless liquid (230 g,corresponding to a yield of 53% theoretical).

Route (II)

All reactions were carried out under a nitrogen atmosphere in a 5-literjacketed reactor fitted with a dropping funnel, a temperature probe anda condenser.

(a) 95% pure diethyl phosphine (400 g, 4.2 moles) was charged to thereactor and heated to reflux (78° C.). 1,2-dibromoethane (244 g, 1.9moles, i.e. 10% excess of diethylphosphine) was charged to the droppingfunnel and then added, over 4 hours, to the refluxing mixture. Theliquid turned cloudy after 30 minutes and became more and more viscousover the addition period. The viscous slurry was heated to 78° C. for atotal period of 3 days.

(b) The slurry was cooled to 70° C. and water (11) added. ³¹P N.M.R.showed:

tetra-ethyl-bis phosphonoethyl-phosphonium ion 72%

 A pH-probe was fitted to the reactor and sodium hydroxide solutionadded slowly until the pH of the contents reached 10. Three layers hadformed.

(c) ³¹P N.M.R. showed the bottom layer to contain both cyclic andlong-chain polymers. The middle layer was found to comprise mainly aphosphonium species of formula:

 where Et=ethyl. The top layer contained the desiredtetra-ethyl-bisphosphonoethyl-phosphonium ion (TEBPE) together withdiethylphosphine. This layer was removed and weighed, giving 530 g,which corresponds to 442 g TEBPE (68% yield of theoretical).

(d) The top layer was transferred to a vacuum-distillation apparatusfitted with a Perkin-triangle fractionating column. The diethylphosphinewas distilled off at atmospheric pressure. A vacuum was then applied bymeans of an oil-pump and the product distilled off at 90-95° C. as acolourless liquid.

EXAMPLE 6 Synthesis of dibutyl phosphine

THPC (75% aqueous solution, 500 g, 2 moles) and ethanol (300ml) werecharged to a 5-liter reactor. A solution of sodium hydroxide (79 g) inwater (79 g) was added over 30 minutes, keeping the temperature below30° C. and the pH below 8. Butyl bromide (620 g, 4.5 moles) was addedand the mixture heated to 65° C. for 4 hours. Sodium hydroxide (102 g)in water (102 g) was charged to a dropping funnel and added in portionsto the contents of the reactor, increasing, the pH by 0.5 every 45minutes. After addition of the sodium hydroxide solution, heating wascontinued for 2 hours. ³¹P N.M.R. at this stage showed about 80% of thephosphonium species of formula:

where Bu=butyl

The volatile organic components were stripped using a TEFLON®-linedvacuum pump. Water (1l), mineral oil (300ml) and sodium sulphite (1000g, 8 moles) were then added, leading to a pH of 10.9. Phosphoric acidwas added until the pH was about 7. A distillation apparatus was fittedto the reactor and the contents heated to 115° C. Two layers slowlyformed in the receiver flask. After 6 hours, ³¹P N.M.R showed that nophosphonium species remained in the reactor. ³¹P N.M.R. of the top layerin the receiver flask showed it to be 75% dibutylphosphine, theremainder comprising monobutyl phosphine, tributyl phosphine and somehydroxymethyl species.

The layers were separated and the organic layer washed with 75% aceticacid. This removed all the tributylphosphine, leaving behind about 7.5%monobutyl phosphine. The yield of dibutylphosphine was 126 g,corresponding to 40% of theoretical.

EXAMPLE 7 Coupling of di-n-butylphosphine with 1,3-dibromopropane

Dibutylphosphine (126 g, 0.86 moles) was heated to 1000° C. anddibromopropane (0.35 moles, 10% excess of the phosphine) was addedslowly over 6 hours. The solution became cloudy and very viscous. Afterstanding overnight a white solid was obtained. This was melted andstirred at 110° C. for 1 day. ³¹P N.M.R. showed mainly one signal (atabout 12 ppm), most probably the desired bisphosphonium salt. The nextday, the viscous product was heated to 110° C. for 4 hours, after whichwater (1000 ml) was added to give a two-layer system.

³¹P N.M.R. analysis of the top layer showed it to consist mainly ofdibutylphosphine. This layer was removed and weighed, giving 21 gdibutylphosphine, equivalent to a recovery of about 17%.

Sodium hydroxide (40 g) in water (40 g) was added to give a three-layersystem. ³¹P N.M.R. showed the top layer to be the desired product. Themiddle layer was found to contain one polymeric phosphonium species,probably a species having the formula:

where Bu=butyl and Pr=propyl, together with some of the product. As itwas impossible to separate these two species, the whole of the middlelayer was discarded.

The top layer was weighed and found to contain 85 g of tetrabutylbisphosphino propane (92% purity as shown by ³¹P N.M.R.) correspondingto a yield of 67% of theoretical.

What is claimed is:
 1. A method for the production of a primary,secondary or tertiary phosphine having the formula (R)_(a)P(H)_(3−a)where R is an organic group and a is 1, 2 or 3, wherein said methodcomprises the following stages: (i) reacting atris(hydroxyorgano)phosphine (THP) with an organic halogen-containingcompound, of formula R(X)_(n) where: R is selected from the groupconsisting of C₁ to C₂₀ alkyl, alkenyl, alkynyl, alkaryl and styryl; Xrepresents a halogen atom; n is a whole number of from 1 to 4 and said Rincludes at least one aliphatic carbon atom adjacent each said halogenatom;  said stage (i) being carried out at a temperature of less thanabout 90° C. and at ambient pressure and in the presence of a solvent;(ii) reacting the product of stage (i) with a base; (iii) thereafteradding, to the resulting product of stage (ii), sufficient of an acid tomaintain a pH of 6 to 8, removing aldehydes from said product of stage(ii) and adding to said product a material to form a discrete organicphase, followed by distilling or phase-separation to obtain saidprimary, secondary or tertiary phosphine.
 2. The method of claim 1,wherein each hydroxy group present in said THP is attached to the carbonatom which is joined to the phosphorus atom of said THP.
 3. The methodof claim 1, wherein said organic halogen-containing compound is presentin said reaction in a stoichiometric excess amount of up to 10:1 byequivalent weight, relative to said THP.
 4. The method of claim 1,wherein said organic halogen-containing compound is present in saidreaction in an amount of 2:1 to 3:1 by equivalent weight, relative tosaid THP.
 5. The method of claim 1, wherein said stage (i) is carriedout in an inert atmosphere.
 6. The method of claim 5, wherein said inertatmosphere consists essentially of a gas selected from the groupconsisting of nitrogen and argon.
 7. The method of claim 1, wherein saidsolvent is selected from the group consisting of water and water/alcoholmixtures, said solvent being present in an amount sufficient tosolubilise said organic halogen containing compound.
 8. The method ofclaim 1, wherein said group R contains from 2 to 8 carbon atoms.
 9. Themethod of claim 1, wherein said atom X is selected from the groupconsisting of chlorine, bromine and iodine.
 10. The method of claim 1,wherein said organic halogen-containing compound is selected from thegroup consisting of ethyl bromide, butyl bromide, 1,2-dibromo-ethane and1,3-dibromo-propane.
 11. The method of claim 1, wherein said group Rcontains at least one ether-linkage or at least one amino-linkage. 12.The method of claim 1, wherein, in said stage (iii), said removal ofaldehydes is achieved by adding sodium sulphite.
 13. The method of claim1, wherein, in said stage (iii) said acid is selected from the groupconsisting of hydrochloric acid, phosphoric acid and acetic acid. 14.The method of claim 1, wherein, in said stage (iii), said material toform a discrete organic phase consists essentially of a substanceselected from the group consisting of mineral oils and petroleum ethers.15. The method of claim 1, wherein said THP is first obtained byreacting a tetrakis(hydroxyalkyl)phosphonium salt with a base.
 16. Amethod of claim 12, wherein said tetrakis(hydroxymethyl phosphonium saltis selected from the group consisting oftetrakis(hydroxymethyl)phosphonium chloride andtetrakis(hydroxymethyl)phosphonium sulphate.